Participants will take pazopanib (800mg) and trametinib (2mg) by mouth daily for a 28 day cycle.

Drug: Pazopanib

A kinase inhibitor indicated for the treatment of patients with advanced renal cell carcinoma and advanced soft tissue sarcoma who have receive prior chemotherapy.

Other Name: Votrient

Drug: Trametinib

A kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test.

Other Name: Mekinist

Detailed Description:

Trametinib and pazopanib are independently approved for other cancers. Both drugs work to inhibit tumor development in different ways. Combining these drugs may lead to improved disease control. The purpose of this study is to evaluate the effect of the combination of both drugs on advanced gastrointestinal stromal tumors.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria includes:

Age ≥ 18 years

Histologically confirmed diagnosis of advanced GIST

ECOG performance status of 0-1

Measurable disease as per modified RECIST 1.1

Prior disease progression on at least imatinib and sunitinib. Maximum of 3 prior kinase inhibitors allowed for treatment of advanced disease. Patients with prior exposure to pazopanib or MEK inhibitors are not eligible.

Patients must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow-up.

Women of childbearing potential must have a negative urine or blood pregnancy test within 7 days of Cycle 1 Day 1. Fertile men and women of childbearing potential must agree to use effective contraception as defined in Section 7 during the study and for 4 months following the last dose of study drugs in both sexes.

Life expectancy of ≥ 3months

Exclusion Criteria includes:

Prior malignancy.

Central nervous system (CNS) metastases at baseline, with the exception of those patients who have previously-treated CNS metastases (surgery +/- radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria:

are asymptomatic and have no requirement for steroids or enzyme-inducing anticonvulsants in at least 3 months prior to screening.

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding

Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement are not considered to be major surgery).

Evidence of active bleeding or bleeding diathesis.

Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage.

Any serious and or unstable pre-existing medical, psychiatric, or other condition that could interfere with the patient's safety, provision of informed consent, or compliance to study procedures.

Unable or unwilling to discontinue use of prohibited medications listed in Section 5.2.4 for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study.

Treatment with any of the following anti-cancer therapies:

Radiation therapy or tumor embolization within 14 days prior to the first dose of OR

Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug.

Ipilimumab must have been discontinued at least 8 weeks prior to initiation of treatment with trametinib

Administration of any non-oncologic investigational drug within 30 days or five half-lives (whichever is longer) prior to the first dose of study drug.

Any ongoing toxicity from prior anti-cancer therapy that is ≥ Grade 1 and/or that is progressing in severity, except alopecia.

Inability to swallow and retain oral medication

Known or suspected allergy or hypersensitivity to pazopanib, trametinib (GSK1120212), or excipients of the formulations given during the course of this trial.

History of interstitial lung disease or pneumonitis, intracardiac defibrillators, known HIV, active HBV or HCV infections, history of retinal vein occlusion, symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02342600